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Open AccessArticle

Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2

Department of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X7, Canada
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Author to whom correspondence should be addressed.
These two authors contributed equally to this work.
Antioxidants 2019, 8(8), 245; https://doi.org/10.3390/antiox8080245
Received: 17 June 2019 / Revised: 18 July 2019 / Accepted: 24 July 2019 / Published: 26 July 2019
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Abstract

Our group recently published a study demonstrating that deleting the gene encoding the matrix thiol oxidoreductase, glutaredoxin-2 (GRX2), alters the bioenergetics of mitochondria isolated from male C57BL/6N mice. Here, we conducted a similar study, examining H2O2 production and respiration in mitochondria isolated from female mice heterozygous (GRX2+/−) or homozygous (GRX2−/−) for glutaredoxin-2. First, we observed that deleting the Grx2 gene does not alter the rate of H2O2 production in liver and muscle mitochondria oxidizing pyruvate, α-ketoglutarate, or succinate. Examination of the rates of H2O2 release from liver mitochondria isolated from male and female mice revealed that (1) sex has an impact on the rate of ROS production by liver and muscle mitochondria and (2) loss of GRX2 only altered ROS release in mitochondria collected from male mice. Assessment of the bioenergetics of these mitochondria revealed that loss of GRX2 increased proton leak-dependent and phosphorylating respiration in liver mitochondria isolated from female mice but did not alter rates of respiration in liver mitochondria from male mice. Furthermore, we found that deleting the Grx2 gene did not alter rates of respiration in muscle mitochondria collected from female mice. This contrasts with male mice where loss of GRX2 substantially augmented proton leaks and ADP-stimulated respiration. Our findings indicate that some fundamental sexual dimorphisms exist between GRX2-deficient male and female rodents. View Full-Text
Keywords: glutaredoxin-2; sex dimorphism; mitochondrial bioenergetics; reactive oxygen species; glutathionylation glutaredoxin-2; sex dimorphism; mitochondrial bioenergetics; reactive oxygen species; glutathionylation
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Mallay, S.; Gill, R.; Young, A.; Mailloux, R.J. Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2. Antioxidants 2019, 8, 245.

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